The present invention relates generally to peritoneal dialysis. More specifically, the present invention relates to peritoneal dialysis solutions.
It is known to use dialysis to support a patient whose renal function has decreased to the point where the kidneys no longer sufficiently function. Two principal dialysis methods are utilized: hemodialysis; and peritoneal dialysis.
In hemodialysis, the patient's blood is passed through an artificial kidney dialysis machine. A membrane in the machine acts as an artificial kidney for cleansing the blood. Because it is an extracorporeal treatment that requires special machinery, there are certain inherent disadvantages with hemodialysis.
To overcome the disadvantages associated with hemodialysis, peritoneal dialysis was developed. Peritoneal dialysis utilizes the patient's own peritoneum as a semi-permeable membrane. The peritoneum is the membranous lining of the abdominal cavity that due to a large number of blood vessels and capillaries is capable of acting as a natural semi-permeable membrane.
In peritoneal dialysis, a dialysis solution is introduced into the peritoneal cavity utilizing a catheter. After a sufficient period of time, an exchange of solutes between the dialysate and the blood is achieved. Fluid removal is achieved by providing a suitable osmotic gradient from the blood to the dialysate to permit water outflow from the blood. This allows the proper acid-base of electrolytes and fluid balance to be returned to the blood and the dialysis solution is simply drained from the body cavity through the catheter.
A number of dialysis solutions have been utilized and suggested. One of the difficulties with dialysis solutions that are used for peritoneal dialysis is that they are not ideal solutions for maintaining acid base homeostasis. Metabolic acidosis is a catabolic event that can occur in peritoneal dialysis patients.
In this regard, the kidneys play a major role in the maintenance of the acid-base balance. In chronic renal failure, the acid generated from the metabolism of dietary proteins can lead to metabolic acidosis. Metabolic acidosis can have a profound and acute effect on the respiratory, cardiac, and/or nervous systems. Long term consequences of metabolic acidosis include protein malnutrition and skeletal diseases.
Lactate has been utilized in peritoneal dialysis solutions for the purpose of maintaining acid-base balance in peritoneal dialysis patients. Typical commercially available peritoneal dialysis solutions contain 35 to 40 mEq/L of lactate.
These solutions are adequate in maintaining acid-base balance in a number of dialysis patients. However, patients who are deficient in lactate metabolism and/or who also experience or suffer from hepatic failure or shock can develop lactic acidosis. This syndrome includes as characteristic symptoms hyperventilation, abdominal pain, and disturbances in consciousness while the patient receives lactate-containing peritoneal dialysis fluids.
An additional issue with respect to lactate peritoneal dialysis solutions is that a number of in vitro studies performed with peritoneal cells indicate that altered cell function can occur when peritoneal cells are exposed to large concentrations of lactate. These changes in cell function can compromise host defense leading to increased rates of infection and damage to the peritoneal membrane.
In order to address this issue, peritoneal dialysis solutions in which lactate is completely replaced by bicarbonate have been proposed. However, in order to balance total body hydrogen ion content against metabolically generated hydrogen, and to maintain normal plasma carbonic acid and bicarbonate concentrations, it is necessary to use bicarbonate concentrations that are considerably in excess of normal. In this regard, bicarbonate concentration upwards of 38 mM/L are believed to be necessary.
Because it is necessary to maintain the solution at a physiological pH, the requirement of such a high bicarbonate solution requires a partial pressure of carbon dioxide (pCO2) that is at least twice the physiologic pCO2 (e.g., greater than 80 mmHg). Although such a solution may meet the metabolic needs of the patient, such a solution does not provide a physiological environment for the peritoneal cells in contact with the solution. Due to the differences in transport rates between bicarbonate and carbon dioxide, with such a solution, the intracellular hydrogen ion concentration of the cell's lining the peritoneal cavity, as well as those present in the peritoneal cavity, would be severely low placing them at a metabolic disadvantage. This metabolic disadvantage will increase more than would be expected if they share the extracellular environment of normal pH, but a supernormal bicarbonate and pCO2.
There is therefore a need for a peritoneal dialysis solution that adequately addresses the problem of metabolic acidosis associated with end stage renal disease.